What is epigenetics, and what does it have to do with autism?

If you’ve been following autism research in recent years, you have probably read—many times—that familial, or inherited, risk is seldom the whole picture. A few inherited genes are sufficient by themselves to cause autism. But most so-called “autism genes” only increase the risk that an infant will go on to develop this developmental disorder. As is the case in many complex diseases, it appears that autism often results from a combination of genetic susceptibility and environmental triggers.

This is where epigenetics comes in. Epigenetics is the study of the factors that control gene expression, and this control is mediated by chemicals that surround a gene’s DNA. Environmental epigenetics looks at how outside influences modify these epigenetic chemicals, or “markers,” and so affect genetic activity.

It is important to remember that scientists use the term “environment” to refer to much more than pollutants and other chemical exposures. Researchers use this term to refer to pretty much any influence beyond genetic mutation. Parental age at time of conception, for example, is an environmental influence associated with increased risk of autism, as are birth complications that involve oxygen deprivation to an infant’s brain.

Because epigenetics gives us a way to look at the interaction between genes and environment, it holds great potential for identifying ways to prevent or reduce the risk of autism. It may also help us develop medicines and other interventions that can target disabling symptoms. We have written about epigenetics previously on this blog (here and here). So in this answer, I’d like to focus on the progress reported at a recent meeting hosted by Autism Speaks.

The Environmental Epigenetics of Autism Spectrum Disorders symposium, held in Washington, D.C. on Dec. 8, was the first of its kind. The meeting brought together more than 30 leaders in autism neurobiology, genetics and epidemiology with investigators in the epigenetics of other complex disorders to promote cross-disciplinary collaborations and identify opportunities for future studies.

Rob Waterland, of Baylor College of Medicine in Texas, described epidemiological studies and animal research that suggested how maternal nutrition during pregnancy can affect epigenetic markers in the brain cells of offspring.

Julie Herbstman, of Columbia University, described research that associated epigenetic changes in umbilical cord blood with a mother’s exposure to air pollutants known as polycyclic aromatic hydrocarbons (PAHs). PAHs are already infamous for their association with cancer and heart disease.

Rosanna Weksberg, of the Hospital for Sick Kids in Toronto, discussed findings that suggest how assisted reproductive technology may lead to changes in epigenetically regulated gene expression. This was of particular interest because assisted reproduction has been associated with ASD. Taking this one step further, Michael Skinner, of Washington State University, discussed “transgenerational epigenetic disease” and described research suggesting that exposures during pregnancy produce epigenetic changes that are then inherited through subsequent generations.

Arthur Beaudet, of Baylor College of Medicine, discussed a gene mutation that controls availability of the amino acid carnitine. This genetic mutation has been found to be more prevalent among children with ASD than among non-affected children, suggesting that it might be related to some subtypes of autism. Further study is needed to follow up on the suggestion that dietary supplementation of carnitine might help individuals with ASD who have this mutation. Caution is needed, however. As Laura Schaevitz, of Tufts University in Massachusetts, pointed out, studies with animal models of autism suggest that dietary supplementation may produce only temporary improvements in symptoms of neurodevelopmental disorders.

So what does this all mean for research that aims to help those currently struggling with autism? The meeting participants agreed that the role of epigenetics in ASD holds great promise but remains understudied and insufficiently understood. For clearer answers, they called for more research examining epigenetic changes in brain tissues. This type of research depends on bequeathed postmortem brain tissue, and Autism Speaks Autism Tissue Program is one of the field’s most important repositories. (Find more information on becoming an ATP family here).

The field also needs large epidemiological studies looking at epigenetic markers in blood samples taken over the course of a lifetime. One such study is the Early Autism Risk Longitudinal Investigation (EARLI). More information on participating in EARLI can be found here.

Autism Speaks remains committed to supporting and guiding environmental epigenetics as a highly important area of research. We look forward to reporting further results in the coming year and years.

I never here anything about cildren and adults with Fragile X syndrome causeing there Autisum. My son Ean has both. My daughter Fragile X as well. With basically no symptoms. My so is starting to talk a little he mostly uses pics. Why do I never see anything about this???

Why can’t AS fund that all important fully vaccinated vs never vaccinated study of children? This is what the autism community is waiting for,not what you have mentioned above, which really means nothing to us and our sick children.

I think they have pretty much ruled out the vacine idea. My sons not sick he learns differenly than others. Its a missing protien in the brain so Ive been told. The help for the bothersome sytoms of the learning diabilty is coming. Ive met with many genetic doctors everyone is very hopefull. I was told this is a very exciting time for them as they are getting close to an aswer.

Well, this is a baby step in the right direction at least. Maybe now AS will be ready to look at how variations of haplotypes have differential immune responses to environmental stimuli, including vaccines, and how these normal genetic variations in the population can lead to epigenetic diseases like narcolepsy or autism. It’s time to either lead, follow, or get out of the way.

I think it is great that AS held this conference. Some novel, and some less novel, research on specific topics had been discussed. It has been established that air pollution/esp proximity to coal burning power plants can cause every imaginable developmental delay. It has been established that pregnant women should eat a well balanced healthful diet. It is known by every ASD Mom that ASD kids who eat a decent diet are healthier than those who do not. We were all in agreement about these issues prior to the conference.

The discussion of infertility drugs and ASD makes sense. The effects cannot be positive and the long term is totally unknown.

It is good these specifics were discussed but we need accompanying actions. Did AS lobby against the lowering of Hg emissions standards? Now that would be great and it helps kids today. Is AS funding novel and innovative dietary intervention research? No, I wish. AS IS funding a multitude of prenatal environmental research which is great, especially for those who felt their child was born ASD. If you were sick or infected w/ a virus while pregnant and have an ASD child that is an important issue.

Unfortunately if you have a child like mine some big issues were not discussed. Why are healthy typically developing babies suddenly becoming autistic and chronically ill? Why did my son have a febrile seizure after a bunch of vaccines? Why did he lose all his speech only months later? Listen, this is not the deal w/ every ASD kid. But we are talking about so many. To have an environmental ASD conference and not discuss adverse vaccine reactions and regression is so disappointing. You have to deal w/ this and better represent kids like mine.

ASDs (autism spectrum disorders) are hypothesized as one of many adaptive human cognitive variations that have been maintained in modern populations via multiple genetic and epigenetic mechanisms. Introgression from “archaic” hominids (adapted for less demanding social environments) is conjectured as the source of initial intraspecific heterogeneity because strict inclusive fitness does not adequately model the evolution of distinct, copy-number sensitive phenotypes within a freely reproducing population.

Evidence is given of divergent encephalization and brain organization in the Neanderthal (including a ~1520 cc cranial capacity, larger than that of modern humans) to explain the origin of the autism subgroup characterized by abnormal brain growth.

Autism and immune dysfunction are frequently comorbid. This supports an admixture model in light of the recent discovery that MHC alleles (genes linked to immune function, mate selection, neuronal “pruning,” etc.) found in most modern human populations come from “archaic” hominids.

Mitochondrial dysfunction, differential fetal androgen exposure, lung abnormalities, and hypomethylation/CNV due to hybridization are also presented as evidence.

Some say, autism may have been caused by epigenetic changes invoked by the conative hypertrophic ambitions of the maternal ancestral line.

In layperson’s terms, the human race is evolving more quickly in places due to successive generations of improving nutrition, lack of periods of starvation, ever-stronger beliefs in the constancy of the food supply. These places are where ASD’s emerge.

Of course, we are constantly supplied with food from an early age so we never actually go on to evolve into successful homotrophs.

–“why it doesn’t occur in mammals that are more like us, rather than just the Damaraland Mole Rat?”

It requires a combination of highly unlikely traits to make a eusocial colony, despite the fact that they do better, in the long run, than non-eusocials:

“eusociality is not a marginal phenomenon in the living world. The biomass of ants alone composes more than half that of all insects and exceeds that of all terrestrial nonhuman vertebrates combined1. Humans, which can be loosely characterized as eusocial2, are dominant among the land vertebrates. The ‘superorganisms’ emerging from eusociality are often bizarre in their constitution, and represent a distinct level of biological organization”http://www.nature.com/nature/journal/v466/n7310/full/nature09205.html

–What is it about modern life that has caused some humans to undergo the same changes as mole rats?

Agriculture was probably the big shift:

“The occurrence of a minimum and necessary combination of pre-adaptive traits, causing the groups to be tightly formed. In animals at least, the combination includes a valuable and defensible nest.
The appearance of mutations that prescribe the persistence of the group, most likely by the silencing of dispersal behaviour. Evidently, a durable nest remains a key element in maintaining the prevalence. Primitive eusociality may emerge immediately due to spring-loaded pre-adaptations.”http://www.nature.com/nature/journal/v466/n7310/full/nature09205.html

–Also, for how long do you estimate that autism has been with us, according to your eusocial hypothesis?

Humanity has probably benefited from (and, hence, maintained) introgressed phenotypes for as long as we’ve had civilizations that were so large and complex that they required a minority of socially decoupled individuals to keep the machiavellians in check. Neanderthal DNA is probably not behind every case of autism. Most West Asian MHCs contain Denisovan DNA: https://en.wikipedia.org/wiki/Denisova_hominin#Interbreeding_with_modern_humans

You posted Rosanna Weksberg, of the Hospital for Sick Kids in Toronto, discussed findings that suggest how assisted reproductive technology may lead to changes in epigenetically regulated gene expression. This was of particular interest because assisted reproduction has been associated with ASD. Would you be able to tell me where I could find more information about the association of assisted repeoductive technology to ASD? We used it to conceive our triplets and they are all on the spectrum. Is Rosanna Weksberg’s research published?
The idea of epigenetics role fascinates me. The Environmental Epigenetics of Autism Spectrum Disorders symposium, held in Washington, D.C. on Dec. 8, was the first of its kind. Do you know if they plan on holding another in the future? I’m so glad you posted this. Thanks.